A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

<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

VRG50635, an experimental oral therapy being developed by <a href="https://www.vergegenomics.com">Verge Genomics</a> for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), was found to be safe and well-tolerated in healthy volunteers, new Phase 1 trial data show.
Top-line data from the <a href="https://www.isrctn.com/ISRCTN14792372">trial (ISRCTN14792372)</a> also showed a promising tolerability and pharmacological profile supporting once-daily dosing.
The company is now planning to advance the treatment into a proof-of-concept study in people with <a href="https://alsnewstoday.com/sporadic-als/">sporadic</a> and <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> that’s expected to start in the final months of 2023.
“We are extremely encouraged by these initial results which highlight the favorable safety and tolerability profile of VRG50635,” Diego Cadavid, MD, chief medical officer of Verge, said in a <a href="https://www.businesswire.com/news/home/20230615018038/en/Verge-Genomics-Announces-Positive-Safety-and-Tolerability-Data-from-the-Phase-1-Clinical-Trial-of-VRG50635-a-Potential-Best-in-Class-Therapeutic-for-All-Forms-of-ALS">company press release</a>.
[recommended-reading id=21684]
<h3>VRG50635 works to block PIKfyve, identified by AI as therapeutic target</h3>
VRG50635 is a small molecule designed to block the PIKfyve protein, a potential therapeutic target in ALS. PIKfyve was identified by the company’s artificial intelligence (AI) platform after sorting a large amount of biological data stemming from brain and spinal cord samples of ALS patients.
The protein is thought to play a role in the endolysosomal pathway, a kind of recycling system inside cells that helps break down faulty or unneeded molecules to keep the cells clean and functioning properly.
In ALS patients, this recycling system is usually not working as needed, leading to the buildup of toxic protein clumps — a hallmark of the disease known to contribute to the death of motor neurons and the progression of <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>. Motor neurons are the nerve cells that control muscle movement and are progressively lost in ALS.
VRG50635 <a href="https://alsnewstoday.com/news/verge-starts-first-human-trial-pikfyve-inhibitor-als/">advanced from discovery</a> to a first-in-human trial in four years. In the lab, it extended survival of nerve cells from ALS patients and models of motor neuron degeneration.
“The lack of predictive animal models is one of the greatest challenges to developing effective ALS therapies today,” said Alice Zhang, CEO and co-founder of Verge. “This is why we’re excited to advance VRG50635, a drug derived directly from human data, into trials in people with ALS.”
The Phase 1 trial tested VRG50635 versus a placebo in 80 healthy adult volunteers. The therapy was given at different doses once or multiple times over one week, starting with a low dose of 60 mg and gradually increasing it up to 1,800 mg in subsequent groups.
There were no serious side effects, and VRG50635 was considered safe. The therapy was also deemed well-tolerated at the highest planned dose.
Data also showed the maximum concentration of VRG50635 in the body and the total exposure to the drug increased in proportion to the dose. Its active metabolite had a half-life (the time taken for its concentration to reduce by half) of about 37 hours, suggesting that VRG50635 may be taken by mouth once daily.
[recommended-reading id=84924]
<h3>Data to be presented at upcoming European conference in Barcelona</h3>
More detailed data will be presented at the upcoming European Network to Cure ALS (ENCALS) 2023 meeting, which will be held July 12-14 in Barcelona, Spain.
“We look forward to sharing additional information at the ENCALS meeting in Barcelona next month and anticipate progressing to a proof-of-concept study in patients with sporadic and familial ALS later this year,” Cadavid said.
According to Zhang, the study is “designed to overcome historical challenges in ALS clinical trials by using state of the art technology, such as digital at-home devices and blood-based biomarkers, that can capture richer, higher-fidelity patient data and have the potential to detect efficacy with greater sensitivity.”

Tag: oral therapy

Clinical trial of oral ALS therapy SPG302 is enrolling in Australia

Potential ALS therapy, VRG50635, found to be safe in healthy adults