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Rapamycin, an approved medication used to prevent organ rejection after a kidney transplant, didn&#8217;t increase the number of <a href="https://alsnewstoday.com/tregs/">regulatory T-cells</a> in adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who are taking part in a Phase 2 clinical trial.
Along with not meeting its primary goal, <a href="https://clinicaltrials.gov/study/NCT03359538">RAP-ALS (NCT03359538)</a> also failed to meet a number of secondary measures. The findings may have been impacted by the COVID-19 pandemic, which prevented many blood samples from being collected, and more trials may be needed to support the effectiveness of rapamycin, which was deemed generally safe and well tolerated.
“Rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS,” the researchers wrote in “<a href="https://www.nature.com/articles/s41467-023-40734-8">Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis</a>,” which was published in <a href="https://www.nature.com/ncomms/">Nature Communications</a>. The study was funded in part by <a href="https://www.pfizer.com">Pfizer</a>, which markets an approved version of rapamycin called <a href="https://www.pfizer.com/products/product-detail/rapamune">Rapamune</a> (sirolimus).
While the exact <a href="https://alsnewstoday.com/causes-of-als/">causes behind ALS</a> are not clear, several disease processes are common to most patients. For example, most have an abnormal accumulation of proteins such as TDP-43 or SOD1 that form clumps outside the nucleus of nerve cells, triggering inflammation and damage.
[recommended-reading id=86683]
<h3>What does rapamycin do in ALS?</h3>
Rapamycin is believed to help nerve cells eliminate these toxic clumps by activating something called autophagy, a process cells use to recycle abnormal components or molecules that are no longer needed.
It also may increase the production of regulatory T-cells (Tregs), immune cells that regulate the excess activity of the immune system. These are often reduced and poorly active in ALS, and disease progression actually tends to occur faster in ALS patients with fewer Tregs, so increasing their amount has been an important consideration for new treatments.
To see if rapamycin could indeed impact the number of Tregs and other disease processes in ALS patients, researchers launched the RAP-ALS trial, which enrolled 63 participants across seven centers in Italy. They were randomly assigned to receive one of two doses of rapamycin — 1 or 2 mg per square meter of body surface area (mg/m2) — or a placebo, given daily for 18 weeks (about four months).
All continued to receive a stable dose of riluzole (sold as <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a>, <a href="https://alsnewstoday.com/tiglutik-riluzole-oral-suspension/">Tiglutik</a>, and <a href="https://alsnewstoday.com/exservan-riluzole-oral-film/">Exservan</a>) during the trial, the main goal of which was to determine if more patients on rapamycin than a placebo saw a positive response — defined as an increase of at least 30% in the number of Tregs from the trial’s start (baseline) to week 18.
The proportion of patients showing a positive response was higher among those who received rapamycin at 1 or 2 mg/m2 versus a placebo (28 and 20% vs. 12%), but the difference wasn&#8217;t significantly different. Similar observations were made after correcting the results for sex, disease duration, rate of decline, and previous treatment with <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone).
Patients in all three groups saw a decline in the ALS Functional Rating Scale Revised (ALSFRS-R), a measure of disease severity where lower scores indicate more severe disease, for up to 54 weeks (about one year). The placebo group tended to progress at a faster rate than patients given the active treatment, but the differences between the groups weren&#8217;t significant.
<h3>Changes in inflammatory molecules, immune cells</h3>
Other secondary efficacy outcomes included changes in inflammatory molecules and in the activation and traveling ability of various immune cells.
The inflammatory cytokine interleukin (IL)-18 was significantly reduced with rapamycin compared with a placebo at week 18, indicating less inflammation, but the effect was lost after treatment stopped.
Rapamycin also significantly increased the numbers of certain immune cells such as monocytes and switch memory B-cells, a type of immune that may produce antibodies upon reactivation, suggesting “a compensatory mechanism of controlling inflammation by B cells,” wrote the researchers, who noted the findings “should be interpreted cautiously and require confirmation in larger studies, considering&#8221; corrections for multiple tests weren&#8217;t applied.
While the lower dose of rapamycin reached stable levels in the blood throughout the 18 weeks, the higher dose peaked at higher than desired levels, which required the next doses to be adjusted.
At week 18, rapamycin wasn&#8217;t detected in samples of the liquid that flows in and around the brain and spinal cord, called the cerebrospinal fluid, indicating it can&#8217;t enter the brain and reach the affected nerve cells.
The proportion of patients who had one or more side effects was similar in the rapamycin and placebo groups (55% vs. 52%), as was the proportion of those with serious side effects (19% for both).
Side effects related to the skin, such as redness, itching, and rash, were about five times as common with rapamycin than with the placebo. A case of acute hepatitis (liver inflammation) was reported in one patient and was likely related to the higher dose, but no lasting consequences were reported.
“In conclusion, this trial demonstrated that treatment with a low dose of rapamycin is safe in patients with ALS, but it failed to demonstrate an effect of the drug on Treg cells,” the researchers wrote.

Rapamycin fails to raise regulatory T-cell levels in RAP-ALS trial

The National Institutes of Health (NIH) has awarded about $45.1 million toward an expanded access program (EAP) of <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a>, an oral therapy candidate for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The EAP, commonly referred to as compassionate use, will make CNM-Au8 available to U.S. patients who aren&#8217;t eligible for clinical trials that are testing the experimental therapy. It will join two other CNM-Au8 EAP programs that have enrolled more than 200 participants.
The programs are expected to provide additional clinical data to support the safety and effectiveness of CNM-Au8, which will be reviewed by regulatory agencies ahead of an approval.
“This EAP study will give ALS patients who don’t meet the criteria to enroll in a clinical trial an opportunity to try CNM-Au8 as a novel investigational therapy,” Jinsy A. Andrews, MD, a professor of neurology at Columbia University, said in a <a href="https://www.globenewswire.com/news-release/2023/10/05/2755532/0/en/National-Institutes-of-Health-Awards-45-1-Million-NINDS-Grant-for-CNM-Au8-Study-in-ALS.html">press release from Clene Nanomedicine</a>, the therapy’s developer.
The program&#8217;s four-year grant comes from the NIH&#8217;s National Institute of Neurological Disorders and Stroke (NINDS), and is supported by the Accelerating Access to Critical Therapies (ACT) for ALS Act, which was signed into law in 2021. The grant was awarded to <a href="https://clene.com/">Clene</a> in collaboration with Columbia University and <a href="https://www.synapticure.com/">Synapticure</a>.
[recommended-reading id=82702]
<h3>Making CNM-Au8 accessible remotely</h3>
The EAP will be led by Andrews, Eric Anderson, MD, vice president of clinical operations and care delivery at Synapticure, and Benjamin Greenberg, MD, head of medical at Clene.
It will enroll patients in all 50 states, including those in remote and rural areas, via Synapticure’s telemedicine neurology clinic and several nationwide clinics.
The program will monitor CNM-Au8&#8217;s safety, its impact on survival and disease progression, and changes in key disease-related biomarkers.
“Programs like this help to advance research and much-needed innovation in ALS,” Andrews said. &#8220;We are truly excited to be a part of this grant with Clene and Columbia and to support people living with ALS by providing access to treatments that could meaningfully impact the course of their disease.&#8221;
She said Synapticure&#8217;s virtual platform will aid in reaching people in remote areas who haven&#8217;t been able to access investigational treatments like CNM-Au8. “We are grateful to NINDS for recognizing how a virtual platform like Synapticure can provide expanded access programs in a remote capacity,&#8221; Andrews said.
<h3>What is CNM-Au8?</h3>
CNM-Au8 is an oral liquid suspension of gold nanoparticles that&#8217;s believed to slow ALS by supporting the energetic needs of nerve cells and other cells of the nervous system. It can also protect them from oxidative stress, a type of cellular stress implicated in the neurodegenerative disease.
It&#8217;s being investigated in the Phase 2 <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS trial (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, as well as in an arm of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS platform trial (NCT04297683)</a>.
Data from the studies have demonstrated CNM-Au8 is safe and can <a href="https://alsnewstoday.com/news/cnm-au8-seen-to-extend-survival-by-more-than-1-5-years-in-als-trial/">slow disease progression</a> and <a href="https://alsnewstoday.com/news/long-term-survival-benefit-seen-cnm-au8-healey-als-analyses-trial/">extend survival</a> in patients.
“Clene has demonstrated evidence of consistent safety and improved survival for CNM-Au8 across a broad ALS population in two independent Phase 2 trials and an ongoing EAP with up to 3.8 years of follow-up,” Greenberg said. “This new EAP provides access to CNM-Au8 for more people living with ALS and enables the collection of survival, safety, and biomarker data in a population not studied in clinical trials. These data can help provide confirmatory support for the existing trial data Clene has gathered in its clinical trials.&#8221;

New EAP will make CNM-Au8 available outside of trials

<a href="https://akavatx.com/">Akava Therapeutics</a> will soon launch a Phase 1 clinical trial to test AKV9, its investigational therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), in healthy people.
The trial follows the clearance of Akava&#8217;s investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA). It will be AKV9&#8217;s first-in-human study and is designed to evaluate the therapy&#8217;s safety, tolerability, and pharmacological properties of single and multiple ascending doses.
&#8220;The FDA&#8217;s IND approval of AKV9 is a testament to our team&#8217;s dedication and the remarkable potential of our approach. We are thrilled to take this important step forward in the development of a groundbreaking therapy for ALS patients,&#8221; Richard Silverman, PhD, founder of Akava Therapeutics, said in a <a href="https://www.businesswire.com/news/home/20230816654411/en/Akava-Therapeutics-Inc.-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-the-Treatment-of-Amyotrophic-Lateral-Sclerosis">company press release</a>.
ALS is caused by the loss of motor neurons, the nerve cells that control voluntary movements, leading to muscle atrophy and the loss of control over vital functions. The disease affects both upper motor neurons, which send messages from the brain to the spinal cord, and lower motor neurons, the nerve cells that connect the spinal cord to the muscles.
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<h3>What does AKV9 do in ALS?</h3>
Most ALS cases are marked by the toxic buildup of proteins, such as SOD-1 and TDP-43, as well as problems in the function of mitochondria and the endoplasmic reticulum (ER) inside motor neurons. Mitochondria are organelles responsible for generating the cells’ energy. The ER is essential for protein production, modification, and transport.
Some <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatments</a> can help manage the disease and extend survival by a few months. There is no cure is available for ALS, however, but an unmet medical need remains for treatments that can meaningfully slow disease progression.
AKV9 inhibits protein aggregation and has been shown to improve the health of upper motor neurons <a href="https://akavatx.com/science-behind-the-discoveries/#protein-aggregation-is-the-hallmark-of-neurodegenerative-diseases-including-als-protein-aggregation-is-one-of-the-common-causes-of-neuronal-vulnerability-and-degeneration,details-ornithine-aminotransferase-inactivators">via multiple mechanisms</a>. Along with lowering protein clumps, the therapy resulted in increased nerve fiber lengthening and branching, improved mitochondrial and ER integrity, and better motor function <a href="https://alsnewstoday.com/news/novel-compound-reverses-motor-neuron-damage-als-mouse-models/">in an animal model of ALS</a> carrying SOD1 mutations.
Combining AKV9 with the approved ALS therapies riluzole (sold as Rilutek, among others) and edaravone (sold as Radicava and Radicava ORS) <a href="https://alsnewstoday.com/news/experimental-als-treatment-akv9-nu-9-fares-well-mouse-study/">led to even greater improvements</a> in upper motor neuron health in additional experiments in a similar mouse model.
The therapy can also cross the blood-brain barrier, a highly selective membrane that regulates which substances can access the brain and spinal cord from the bloodstream.
“Our goal is to make a meaningful difference in the lives of those affected by neurodegenerative diseases and we are excited about the potential impact of AKV9 in addressing this devastating disease,&#8221; Silverman said.

FDA clears first-in-human clinical trial of AKV9 in healthy volunteers

<a href="https://spinogenix.com/">Spinogenix</a> has launched a clinical trial in Australia to investigate its <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) treatment candidate SPG302 in patients and healthy volunteers.
The first-in-human <a href="https://www.clinicaltrials.gov/study/NCT05882695?term=spinogenix&amp;rank=1">Phase 1 clinical trial (NCT05882695)</a>, which is recruiting up to 112 participants, is being conducted at the Nucleus Network Melbourne, Australia. Its opening follows the approval recently by the Human Research Ethics Committee (HREC) to let Spinogenix initiate clinical studies of SPG302 in the country.
“We are extremely pleased to receive approval from the HREC to proceed with human clinical trials,” Stella Sarraf, PhD, Spinogenix&#8217;s founder and chief executive officer, said in a <a href="https://www.globenewswire.com/news-release/2023/07/10/2701531/0/en/Spinogenix-Receives-Approval-from-the-Australia-Human-Research-Ethics-Committee-to-Initiate-a-Phase-1-Human-Clinical-Trial-of-SPG302-a-Novel-Regenerative-Drug-for-the-Treatment-of-.html">company press release</a>. “These human clinical trials will help us determine safety and tolerability in healthy volunteers and provide early signals of efficacy of our novel, first-in-class drug to help improve the lives of people with ALS.&#8221;
A feature of ALS is the progressive dysfunction and death of motor neurons, the nerve cells that direct voluntary movements, rendering the brain unable to control them. In early disease stages, even before symptoms become evident, motor neurons exhibit a loss of synapses, sites of contact between two nerve cells that enable communication via chemical signals.
The transmission of signals from one cell to the other through synapses is what lets people maintain cognitive and motor functions, which are reduced with ALS and other neurodegenerative diseases.
“There remains an unmet need for new innovative therapeutics for ALS which is almost invariably fatal within [three to five] years of diagnosis. The therapies that are currently approved for ALS provide only a modest extension of life and are not well tolerated by all patients,” Sarraf said.
[recommended-reading id=81519]
<h3>What is SPG302 and what does it do?</h3>
SPG302 is an orally available small molecule designed to increase the number of synapses in nerve cells. Called a spinogenic compound due to its mechanism of action, it&#8217;s led to improvements in <a href="https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP284004">motor</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/34738197/">cognitive function</a> in animal models of neurodegenerative diseases and spinal cord injury.
The therapy can penetrate the blood-brain barrier, a highly selective membrane that prevents most molecules in the blood from reaching the brain, limiting the effectiveness of many potential therapies.
The ongoing Phase 1 trial will evaluate the safety, tolerability, and pharmacological properties of SPG302 in healthy volunteers and people with ALS.
The trial will be conducted in three parts. Part 1 will include healthy volunteers and examine the effects of a single administration of five ascending doses. A group of patients will also be studied to see if food can impact the medication&#8217;s effects.
In Part 2, five groups of healthy volunteers will receive an ascending SPG302 dose daily over five days. In Part 3, patients will receive a once daily dose for about four weeks, after which they may choose to enter an open-label extension study to probe the long-term effects of treatment.
The trial will be placebo-controlled and double-blind, meaning all the participants will be randomly assigned to receive a placebo or SPG302 and neither researchers nor participants will know who receives which.
The therapy’s efficacy, namely its effect on the brain’s electrical activity, biomarkers, respiratory measures, and functional outcomes, will also be assessed.
“We are happy to see that Spinogenix is progressing into human trials. To my knowledge, this is the first clinical trial in ALS focused on regenerating synapses with a small molecule,” Merit Cudkowicz, MD, director of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, said. “It has the potential to be used in combination with many other treatments approved and in development.&#8221;
SPG302 received <a href="https://alsnewstoday.com/news/spinogenix-oral-therapy-spg302-als-awarded-fda-orphan-drug-designation/">orphan drug status</a> by the U.S. Food and Drug Administration (FDA) for treating ALS in 2021. The designation provides certain benefits to accelerate drug development, including tax credits and seven years of market exclusivity if the therapy is approved.

Clinical trial of oral ALS therapy SPG302 is enrolling in Australia

<a href="https://auralanalytics.com/" rel="nofollow">Aural Analytics</a>&#8216; speech analytics software app for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), intended for use by researchers and doctors working in the disease, has been designated a breakthrough device by the U.S. Food and Drug Administration (FDA).
The designation is meant to speed the development and review of devices with a potential to better treat or diagnose life-threatening or chronic and debilitating conditions.
Called <a href="https://appadvice.com/app/speech-vitals/1501374404" rel="nofollow">Speech Vitals</a>, the ALS mobile application collects short samples of a patient&#8217;s speech, prompted by app-based tasks, to help professionals in monitoring changes, from improvements to disease progression.
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<h3>Changes in patient&#8217;s status as evident in short clips of speech</h3>
<h3></h3>
“Achieving breakthrough designation for Speech Vitals &#8211; ALS is explicit validation that the FDA sees the potential in the Speech Vitals platform to provide for more effective management of this devastating disease,” Jeremy Moore, Aural Analytics&#8217; director of quality assurance and regulatory affairs, said in a <a href="https://www.businesswire.com/news/home/20230329005040/en/FDA-Grants-Breakthrough-Device-Designation-to-Aural-Analytics-for-Speech-Analytics-Software-to-Be-Used-in-Treatment-of-ALS">company press release</a>.
“We look forward to working closely with the agency to continue to develop our platform &#8230; to get it into the hands of the physicians and patients that need it the most,” Moore added.
Due to the progressive weakness in the muscles that control the mouth and vocal cords, people with ALS often experience <a href="https://alsnewstoday.com/speech-problems/">speech problems</a> early in their disease course. These include slow or slurred speech, hoarseness, and difficulty managing tone and pitch.
As speaking abilities tend to worsen over time, changes in speech can be noninvasive, ready markers for monitoring disease progression.
&#8220;We strive to improve patient outcomes by unlocking the valuable brain health data available in the speech signal with scientifically sound and technically viable speech analytics technology,&#8221; the company states on its homepage.
The app is reported to be user-friendly and intended for clinic or home use. But its current use may be limited to clinical trial participants as a way of helping to determine an investigative therapy&#8217;s effectiveness.
Aural Analytics reported, in a <a href="https://auralanalytics.com/aural-analytics-speech-technology-signaled-slowing-of-decline-in-als-patients-speech-and-bulbar-function-in-platform-trial-evaluating-pridopidine-strong/" rel="nofollow">separate release</a>, that the app was used in the Phase 2/3 study (<a href="https://clinicaltrials.gov/ct2/show/NCT04615923">NCT04615923</a>) of oral pridopidine, part of the ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS Platform Trial (NCT04297683)</a> that is testing multiple ALS treatment candidates simultaneously.
While the pridopidine <a href="https://alsnewstoday.com/news/pridopidine-shows-some-potential-in-healey-trial-but-misses-main-goal/">trial failed to meet its primary goal</a> of better physical function, recently diagnosed patients with signs of rapidly progressing ALS showed benefits with treatment.
Significant gains also were observed in two speech measures — speaking rate (how fast someone talks) and articulation rate (how quickly and clearly someone sounds out each word) — across treated patients relative to those given a placebo, as were positive trends in respiratory function.
Technology used in the app currently is available on four continents and works with eight languages, Aural Analytics reported.
Speech Vitals collects a few minutes of speech from a patient engaging in tasks that gauge speech duration, precision of articulation, speaking rate, and other metrics that help to monitor motor conditions that affect speech. The app can be deployed on any device, anywhere in the world.
Aural Analytics also intends to explore its technology as a potential tool to help in <a href="https://alsnewstoday.com/als-diagnosis/">diagnosing ALS</a>. Should Speech Vitals &#8211; ALS be given regulatory approval, the company plans to apply the technology to <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a> and other conditions affecting speech.

Speech Vitals, software app for ALS research and care, gains FDA support

<a href="https://www.kadimastem.com/">Kadimastem</a> is planning a Phase 2a clinical trial to test if repeat dosing of AstroRx, its investigational therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), can continuously delay the disease&#8217;s progression.
The study will investigate every three-month dosing after findings from an earlier <a href="https://clinicaltrials.gov/ct2/show/NCT03482050">Phase 1/2 trial (NCT03482050)</a> showed a single infusion led to a clinically meaningful <a href="https://alsnewstoday.com/news/astrorx-safe-slows-als-progression-phase-1-2-clinical-trial/">decline in disease progression</a> over the first three months, but lost effectiveness later on.
The company recently submitted an investigational new drug (IND) application asking the U.S. Food and Drug Administration (FDA) to clear the trial.
“The submission of an IND to the FDA is a major milestone. It is very exciting to have arrived at this juncture. We eagerly await the approval to start this trial and wanting to help ALS patients as soon as possible,” said Michel Revel, MD, PhD, founder and chief scientific officer at Kadimastem, in a <a href="https://www.kadimastem.com/post/kadimastem-submits-ind-application-to-the-fda-for-its-phase-iia-clinical-trial-with-astrorx-for-als">company press release</a>.
[recommended-reading id=78965]
AstroRx is an off-the-shelf, investigational cell therapy composed of healthy astrocytes derived from human embryonic stem cells. Astrocytes are star-shaped cells that support nerve cells in the brain and spinal cord, but are believed to go awry in ALS and contribute to disease progression.
Injected directly into the spinal canal (intrathecal administration), it&#8217;s expected to make up for the faulty astrocytes, preventing further damage to nerve cells and slowing disease progression.
AstroRx&#8217;s safety and preliminary signs of efficacy were investigated in the Phase 1/2 study in Israel, which enrolled 10 patients who&#8217;d been diagnosed with ALS in the past two years.
After an initial monitoring period of three months, patients were equally divided to receive a single dose of 100 million AstroRx cells (low dose) or 250 million AstroRx cells (high dose) and were monitored for up to a year.
Results from the open-label trial showed both doses induced a significant decrease in the rate of disease progression over the first three months — a 53% reduction. However, no benefits were observed in either group after six and 12 months&#8217; follow-up, suggesting repeat dosing is necessary to maintain its efficacy.
“For the last year, we’ve reported our plans to submit an IND to the FDA with AstroRx for the treatment of ALS. The submission of the IND marks a significant milestone for the company, and subject to the approval of the FDA we hope to commence this very important multi-site trial and to bring this potential life enhancing therapy to the market and to patients as soon as possible,” said Ronen Twito, Kadimastem’s board executive chairman.
The investigational cell therapy was granted a U.S. patent <a href="https://alsnewstoday.com/news/als-cell-therapy-maker-kadimastem-awarded-patent-astrorx/">in August 2022</a> for treating ALS and other neurodegenerative diseases. Patents are also in place in Japan and Israel. The company also continues to advance its diabetes program, according to Kadimastem CEO Asaf Shiloni.

Kadimastem asks for FDA to clear new AstroRx clinical trial

Adding a skin patch containing a Chinese herb mixture called Ji Wu Li (JWL) to standard medications significantly slowed disease progression in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to data from a randomized clinical trial.
In the trial, called ALS-CHEPLA (ChiCTR200037353), the benefits of the herbal treatment emerged after eight weeks and were sustained up to 20 weeks, or about five months.
&#8220;Combining [traditional Chinese medicine] formulations with western medicine is an encouraging way to help alleviate symptoms and delay ALS progression,&#8221; the researchers wrote.
The study, &#8220;<a href="https://www.frontiersin.org/articles/10.3389/fneur.2022.990802/full">Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster–The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial</a>,&#8221; was published in <a href="https://www.frontiersin.org/journals/neurology">Frontiers in Neurology</a>.
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<h3>120 patients randomized to herbal or placebo skin patch for 20 weeks</h3>
Despite existing <a href="https://alsnewstoday.com/approved-treatments-for-als/">ALS treatments</a>, there remains a significant need for more effective and less costly medications that slow disease progression.
A number of herbal medicines derived from traditional Chinese medicine have been evaluated in preclinical models and clinical studies of ALS, and some are thought to offer benefits when used as an add-on to standard ALS treatments.
Oral administration of these medicines is limited, however, because of the large amount that&#8217;s required to have an effect. This also can be particularly challenging for ALS patients with bulbar involvement, in whom weakness in the muscles of the face, neck, and tongue can make swallowing difficult.
Transdermal, or on-the-skin, application could offer a way to deliver a concentrated formulation of the medication while avoiding the need for swallowing. Other potential advantages include prolonged release, improved patient adherence, and a minimization of side effects, the researchers noted.
Researchers in China launched the ALS-CHEPLA trial to evaluate the safety, tolerability, and efficacy of transdermal JWL — a mixture of Chinese herbs — against a placebo in ALS patients.
A total of 120 adult patients were recruited at the Shuguang Hospital, in Shanghai, and randomized to either the investigational treatment or a placebo, both administered as a self-adhesive patch on the patient&#8217;s upper back. No significant differences in terms of sex, age, body weight, and disease duration or progression were noted between these two groups at the study&#8217;s start.
Patches were worn on six consecutive days per week for six hours each day, followed by one rest day. This was repeated for a total of 20 weeks. Participants continued using their other regular medications.
Most participants (72) were men, and patients&#8217; mean age was in the mid-50s. Seventy people had limb involvement only, meaning that their symptoms involved weakness in the limbs, whereas 25 had only bulbar involvement, and 25 had symptoms consistent with involvement of both regions.
A majority of the people in each treatment group, 47 of 60, completed the entire 20-week study.
The trial&#8217;s main goal was to assess changes in disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), in which lower scores indicate greater functional impairment.
<h3>Lesser ALSFRS-R score declines seen with use of alternative treatment</h3>
Results showed that JWL treatment significantly slowed disease progression, reflected by a lesser decline in ALSFRS-R scores over the trial&#8217;s five months. The effect began to be observed at eight weeks after the study&#8217;s start and remained significant up to 20 weeks, the researchers reported.
Overall, patients treated with the JWL plaster experienced an average reduction of 4.44 points in their ALSFRS-R scores over 20 weeks, compared with a drop of 5.28 points in the placebo group, amounting to a significant difference of 0.84 points.
Researchers also examined scores on the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatments (ALS-SSIT) — a measure of quality of life that reflects changes in disease severity with the use of traditional Chinese medicines — and in weight loss as secondary outcomes.
Quality of life declines were slower among JWL-treated patients than those on a placebo patch, again reaching significance starting at eight weeks of treatment and lasting through week 20.
While all patients progressively lost weight throughout the trial, those using the JWL patch lost significantly less weight overall at week 20 compared with those on a placebo.
Local allergic reactions at the patch site were observed in 10 patients given JWL and nine given placebo, all of which were mild or moderate in severity and resolved after stopping the plaster treatment. A total of seven people in the JWL group and five in the placebo group discontinued treatment due to this side effect.
&#8220;Skin reactions were the only adverse effects leading to trial cessation in this study. However, the termination rate in the JWLP group was half the rate reported for <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">riluzole</a>, and the adverse events were less severe,&#8221; the researchers wrote.
Other observed side effects included fever, sore throat, nausea, and constipation, all of which were temporary and deemed not related to treatment.
The researchers noted that the benefits of the treatment were likely due to the herbs&#8217; effects on biological processes known to be disrupted in ALS. &#8220;Overall, the ingredients of every single herb of JWL have effects on almost all known mechanisms of ALS,&#8221; the researchers wrote.
Trial findings overall suggest &#8220;[JWL] offers a promising add-on therapy for ALS, particularly in patients with bulbar involvement,&#8221; the team wrote, noting that future studies should aim to optimize the treatment patch to avoid skin reactions, and to learn more about how the herbal ingredients are absorbed in the body.

Tag: ALS clinical trial