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<a href="https://coavetx.com/">Coave Therapeutics</a> has received a grant from the <a href="https://www.als.org/">ALS Association</a> to support the development of its gene therapy candidate CTx-TFEB for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The grant, made through the <a href="https://www.als.org/research/research-we-fund/our-awards-and-programs/barnett-drug-development-program">Lawrence and Isabel Barnett Drug Development Program</a>, is part of the $2.9 million the ALS Association has granted to six organizations committed to advancing novel therapies for ALS.
It will help the company conduct proof-of-concept preclinical studies of CTx-TFEB that may support moving the treatment into ALS clinical trials in the future.
“Our goal is to establish a robust preclinical proof-of-concept, laying a strong foundation for advancing to the clinic in the near future,” Lolita Petit, PhD, Coave’s chief scientific officer, said in a <a href="https://www.globenewswire.com/news-release/2024/02/29/2837821/0/en/Coave-Therapeutics-Receives-Grant-from-the-ALS-Association-to-Advance-its-CTx-TFEB-Program-as-a-Potential-Treatment-for-All-Forms-of-ALS.html">company press release</a>. “Together, we are now on the brink of a breakthrough that promises hope and progress for patients impacted by ALS.”
[recommended-reading id=89823]
<h3>Importance of moving promising treatments from laboratory to clinical testing</h3>
“Getting promising treatments out of the laboratory and into clinical testing as quickly as possible is key to making ALS a livable disease until we can cure it,” said Kuldip Dave, PhD, senior vice president of research at the ALS Association.
The molecular mechanisms that cause ALS aren&#8217;t fully known, but virtually all cases are marked by the accumulation of protein clumps. This is in part due to a dysregulation in autophagy — the process by which cells recycle abnormal or defective molecules, which usually happens inside specialized compartments called lysosomes.
It&#8217;s anticipated that boosting autophagy could promote the clearance of these toxic protein clumps in ALS nerve cells, thereby slowing or halting neuronal degeneration and disease progression.
The transcription factor TFEB has emerged as a key regulator of the autophagy lysosomal pathway. This protein is found at lower levels in the brains of ALS patients, and activating it is believed to be a promising approach to increase autophagy and remove the harmful protein clumps.
CTx-TFEB is a novel genetic therapy product designed to deliver the TFEB gene specifically to nerve cells in the brain and spinal cord. The gene sequence is transported inside an adeno-associated virus that does not cause disease in humans. The virus was modified with Coave’s proprietary <a href="https://coavetx.com/#meetaligater">ALIGATER platform</a> to carry certain molecules that make the vector more specific to nerve cells.
“Modulating autophagy using TFEB gene therapy is an exciting approach to promote the clearance of accumulated toxic material in affected neurons, halt motor neuron degeneration, and preserve muscular function in people with ALS,” Petit said.
The therapy is expected to activate autophagy in ALS patients regardless of their genetic subtype, potentially serving as a therapy for all <a href="https://alsnewstoday.com/forms-of-als/">types of ALS</a>.
“We are proud to help drive the crucial transition from preclinical to clinical development for potential new ALS therapies through our Lawrence and Isabel Barnett Drug Development Program,” Dave said.

Coave wins grant to advance gene therapy CTx-TFEB for ALS

<a href="https://myrotx.com/">Myrobalan Therapeutics</a> will use a $400,000 grant from the <a href="https://www.als.org/">ALS Association</a> — along with $24 million in new financing — to help advance the development of its oral CSF1 receptor (CSF-1R) inhibitor program, intended to reduce neuroinflammation and promote nerve repair in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The ALS Association grant was awarded via the nonprofit&#8217;s Lawrence and Isabel Barnett Drug Development Program, which supports the preclinical evaluation of new and repurposed therapies for the neurodegenerative disorder. It follows on the heels of a <a href="https://myrotx.com/news-events/myrobalan-therapeutics-completes-series-a-financing-of-24-million-to-develop-potentially-first-in-class-cns-therapeutics-with-restorative-potential/">Series A funding by Myrobalan</a> last month that raised nearly a quarter of a billion dollars to further the development of the company&#8217;s treatment program for people with ALS.
Myrobalan&#8217;s CSF-1R inhibitor program was specifically designed for use in diseases of the central nervous system, or CNS, which comprises the brain and spinal cord. The company is advancing the clinical biomarker strategy toward the first clinical trial of its CSF-1R inhibitor, which is expected to start next year, according to a <a href="https://www.businesswire.com/news/home/20240206866405/en/Myrobalan-Therapeutics-Receives-a-Grant-from-the-ALS-Association-to-Advance-its-CSF1R-Inhibitor-Program">Myrobalan press release</a>. The new monies will keep the program on track, according to the release, which said Myrobalan was &#8220;very pleased to receive this grant from the ALS Association.&#8221;
“This recognition affirms Myrobalan’s commitment to CNS drug development and empowers us to enhance our development efforts with respect to CSF-1R and ALS,” said Jing Wang, PhD, the company&#8217;s CEO and co-founder.
&#8220;Ultimately, our goal is to make a CSF-1R inhibitor therapy accessible to all patients grappling with ALS,&#8221; Wang said.
[recommended-reading id=86121]
<h3>Myrobalan aiming for 1st clinical trial of CSF-1R inhibitor next year</h3>
ALS is characterized by the progressive death of motor neurons, the nerve cells that control muscle movement. Loss of these neurons leads to <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> like muscle weakness and wasting, with a progressively worsening impact on a patient&#8217;s ability to perform tasks of daily living.
Although <a href="https://alsnewstoday.com/causes-of-als/">its causes</a> are largely unknown, several bodily systems are dysregulated in ALS, contributing to the disease&#8217;s onset and progression. Known ALS-related processes include inflammation of the brain — neuroinflammation — and demyelination, or the loss of the myelin sheath that protects nerve fibers and helps them send signals efficiently.
Causing these processes are alterations in microglia, the CNS’ resident immune cells, and myelin-producing cells called oligodendrocytes.
The company is working on oral, small molecule CSF-1R inhibitors. Myrobalan&#8217;s hypothesis is that intermittent treatment with CSF-1R inhibitors depletes microglia — whose ability to adapt is then impaired, thereby reducing inflammation and allowing remyelination, or the formation of new myelin.
[quote=&#8221;center&#8221;]We are proud to help drive the crucial transition from preclinical to clinical development for potential new ALS therapies.[/quote]
According to Myrobalan, its CSF-1R inhibitor program was specifically designed for central nervous system diseases, and has shown potency, selectivity, and favorable CNS distribution in preclinical studies.
The ALS Association award, granted to scientists worldwide, is part of the nonprofit&#8217;s philanthropic funding.
“We are proud to help drive the crucial transition from preclinical to clinical development for potential new ALS therapies,” said Kuldip Dave, PhD, ALS Association’s senior vice president of research.
“Getting promising treatments out of the laboratory and into clinical testing as quickly as possible is key to making ALS a livable disease until we can cure it,” Dave said.
In addition to ALS, Myrobalan plans to develop its CSF-1R inhibitors for other neurodegenerative indications, such as <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a> and <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s disease</a>. The company also is developing other compounds to reduce microglia-driven neuroinflammation and improve remyelination.

$400K ALS Association grant will advance CSF-1R inhibitor program

<a href="http://dewpointx.com">Dewpoint Therapeutics</a> has received a grant from the <a href="https://www.targetals.org/">Target ALS Foundation</a> to advance the development of small molecules called c-mods, which will target the TDP-43 condensates thought to drive most cases of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
Condensates are borderless compartments in cells that can cause cellular processes to go awry, leading to a so-called condensatopathy. In ALS, TDP-43 condensates are linked to multiple markers of disease.
“Receiving the Target ALS grant is a tremendous honor and a significant validation for Dewpoint’s novel, therapeutic approach to target condensatopathies,” Ameet Nathwani, MD, Dewpoint’s CEO, said in a <a href="https://www.globenewswire.com/news-release/2024/01/16/2809938/0/en/Dewpoint-Therapeutics-Awarded-Target-ALS-Grant-for-Development-of-C-mods-for-ALS.html">company press release</a>.
“This grant will propel our research efforts and accelerate the development of our ALS-targeted c-mods towards becoming the first molecules to address the underlying pathology [disease mechanism] in most ALS patients,” Nathwani said.
[recommended-reading id=82931]
<h3>Grant to support proof-of-concept study using mouse model of ALS</h3>
The in-kind grant, awarded in collaboration with the <a href="https://www.als.org">ALS Association</a> and <a href="https://www.jax.org/">The Jackson Laboratory</a>, will support an in vivo proof-of-concept study of the company’s c-mods in a mouse model of ALS.
The TDP-43 protein normally resides in the nucleus, the cells’ control center that harbors most of the genetic material. In ALS, however, TDP-43 moves outside the nucleus and clumps into toxic condensates that prevent nerve cells from working properly, causing <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>.
“Cellular mislocalization [incorrect or faulty localization] and aggregation of TDP-43 is the pathological hallmark of 97% of ALS cases, however, no marketed drugs target TDP-43 directly,” said Amy Easton, PhD, Target ALS Foundation’s senior director of scientific programs.
Dewpoint identified small molecules that can move mislocalized TDP-43 back into the nucleus. These small molecules, which the company <a href="https://www.frontiersin.org/articles/10.3389/fmolb.2022.1007744/full">dubbed c-mods</a> (from condensate-modifying drugs), are expected to rescue damage to nerve cells and ease symptoms.
In cell models of ALS, the company has demonstrated <a href="https://dewpointx.com/modulation-of-tdp-43-condensates-rescues-als-ftd-disease-phenotypes-in-multi-stressor-paradigms-presented-at-icgeb-conference-on-tdp-43-function-and-dysfunction-in-disease/">c-mods can reverse some of the cellular changes</a> induced by the aberrant TDP-43 protein clumps, including alterations in gene activity and stress-induced damage.
With support from the grant, Dewpoint will now test whether c-mods can similarly ease disease processes in a mouse model of ALS. This model carries a repeat expansion of a short DNA sequence in the C9orf72 gene, the most common genetic mutation in <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial</a> and <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a>.
“Dewpoint’s research proposal, reviewed by the Target ALS Independent Review Committee, included a high-quality preliminary data package, sufficient to trigger in vivo studies in a disease model,” Easton said.
“Dewpoint’s study is one of the first to test whether reducing TDP-43 condensates is beneficial in the context of a C9orf72 repeat expansion, the most common <a href="https://alsnewstoday.com/causes-of-als/#Genetics_of_ALS">genetic cause of ALS</a>,” Easton added.
The company also recently filed multiple patent applications to cover c-mods and their use in ALS and other TDP-43-mediated conditions. Over the next few years, it is expected to produce multiple additional c-mods to target a number of other conditions, according to another company <a href="https://www.globenewswire.com/news-release/2024/01/07/2805015/0/en/Dewpoint-Therapeutics-Filed-Multiple-Patent-Applications-with-the-US-Patent-Office-on-Novel-Composition-of-Matter-for-the-Treatment-of-ALS.html">press release</a>.

Dewpoint wins grant to develop its condensate-modifying therapies

The <a href="https://www.als.org/">ALS Association</a> has given <a href="https://www.oryzon.com/en">Oryzon Genomics</a> nearly $500,000 to advance ORY-4001, a potential treatment of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), into preclinical studies.
The $498,690 grant was provided via the association&#8217;s Lawrence and Isabel Barnett Drug Development Program. Oryzon intends for laboratory studies in mouse disease models to pave the way for ORY-4001 to be tested in clinical trials.
&#8220;We are proud to help drive the crucial transition from preclinical to clinical development for potential new ALS therapies like ORY-4001,&#8221; Kuldip Dave, PhD, senior vice president of research at the ALS Association, said in an <a href="https://www.globenewswire.com/news-release/2023/12/04/2789939/0/en/ORYZON-Awarded-with-a-Grant-for-ORY-4001-From-the-ALS-Association-in-the-U-S.html">organization press release</a>.
&#8220;Getting promising treatments out of the laboratory and into clinical testing as quickly as possible is key to making ALS a livable disease until we can cure it,” Dave added.
[recommended-reading id=88415]
<h3>ALS Association grant supports work needed to bring ORY-4001 into a trial</h3>
ORY-4001 is a highly selective inhibitor of histone deacetylase 6 (HDAC6), part of a family of enzymes that regulate cellular activity through a chemical modification to proteins called deacetylation.
HDAC6 has been linked to cellular processes involved in neurodegenerative disease, and blocking it has emerged as a possible treatment strategy for conditions such as ALS.
Particularly, HDAC6 activity regulates alpha tubulin, a protein involved in cellular protein transport. Impaired axonal transport — the movement of proteins needed for nerve cell health and survival along a cell&#8217;s fiber-like projections (axons) — is a feature of ALS and other neurological diseases.
Preclinical studies have shown that HDAC6 inhibition <a href="https://alsnewstoday.com/news/resolving-traffic-jams-in-human-als-motor-neurons/">protects against axonal transport deficits</a> in models of ALS and may be able to slow neurodegeneration.
Oryzon has been evaluating the therapeutic potential of various HDAC6 inhibitors for neurological diseases, and earlier this year selected ORY-4001 as its clinical development candidate.
The therapy&#8217;s initial development efforts have been focused on <a href="https://charcot-marie-toothnews.com/charcot-marie-tooth-type-1-cmt1/">Charcot-Marie-Tooth disease type 1</a> (CMT1), an inherited disease affecting peripheral nerves, those that participate in communication between the brain and the rest of the body.
<h3>Therapy showed potential in model of disease also marked by muscle wasting</h3>
In a mouse model of CMT1, the molecule improved neuromuscular function, prevented axon damage, and prevented the loss of <a href="https://multiplesclerosisnewstoday.com/myelin-sheath/">myelin</a>, the substance that surrounds and protects nerve cell axons, Oryzon reported.
Both CMT1 and ALS are characterized by muscle weakness and wasting, as well as altered axonal transport. Disturbed proteostasis, the process by which proteins are regulated to maintain cellular health, also is evident in both conditions.
Given this overlap and previous preclinical studies of HDAC6 inhibitors in ALS, the scientists believe ORY-4001 may be a promising treatment candidate.
&#8220;The rationale linking ORY-4001’s mechanism of action to the disease is sound,&#8221; said Jordi Xaus, PhD, Oryzon&#8217;s chief scientific officer.
In addition to testing ORY-4001 in an ALS mouse model, the company is conducting the toxicology studies required before a therapy can be tested in humans.
&#8220;If these preclinical results are positive, we plan to extend the clinical development of ORY-4001 … to include ALS and explore its therapeutical potential for people living with this devastating disease,&#8221; Xaus said.
&#8220;It is an honor to have the support of the ALS Association,&#8221; he added.

ALS Association helping to move ORY-4001 into animal studies

A new two-year, $400,000 grant will support studies — by <a href="https://www.everythingals.org/">EverythingALS</a> and the <a href="https://www.massgeneral.org/neurology/als">Sean M. Healey and AMG Center for ALS</a> at Massachusetts General Hospital (MGH) — aimed at identifying early digital diagnostic markers in <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The award, from <a href="https://www.alsfindingacure.org/">ALS Finding a Cure</a> and the <a href="https://www.als.org/">ALS Association</a>, is backing the development of the NeuroLens Digital Diagnostics program. A diverse and multidisciplinary research partnership, NeuroLens seeks to remotely monitor presymptomatic ALS gene carriers — individuals at a high genetic risk for developing the neurodegenerative disorder who are not yet showing any of its signs.
The overarching goal is to spot early <a href="https://alsnewstoday.com/als-symptoms/">signs and symptoms of ALS</a>, ensuring patients receive a definite diagnosis and <a href="https://alsnewstoday.com/als-treatment/">ALS treatment</a> as soon as is possible, which has the potential to improve outcomes. On average, an <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a> now takes 12 to 18 months.
&#8220;We&#8217;re thrilled to launch the NeuroLens digital diagnostics initiative and the grassroots efforts to build and strengthen the ALS community and encourage collaboration across groups working toward the shared goal of finding early diagnosis of this devastating disease,&#8221; Indu Navar, EverythingALS founder, said in a <a href="https://www.businesswire.com/news/home/20230822233607/en/New-400000-Grant-Supports-EverythingALS.org-and-Mass-General-Hospital-MGH-to-Develop-NeuroLens-a-Digital-Diagnostics-technology-initiative-for-early-detection-of-Amyotrophic-Lateral-Sclerosis-ALS">press release</a>.
&#8220;This open source organizing model for ALS could be transformational as we can share data and collaborate with thousands of researchers and AI engineers. This brings hope to the ALS community and their loved ones who are tackling enormous challenges and hoping for movement and momentum,&#8221; Navar added.
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<h3>Seeking diagnostic markers to track ALS gene carriers, family members</h3>
The novel diagnostics program is a decentralized and open innovation platform to remotely and continuously monitor gene carriers and their blood relatives who are at high risk of developing the progressive disorder but don&#8217;t yet have symptoms.
Globally, the gene carriers and family members will be monitored digitally — no doctor visits are necessary — with the help of sensors that assess functional changes in daily activities such as climbing and walking, and in speech and cognition. Videos will be used to capture subtle facial changes that can accompany ALS development.
The scientists then will use data derived from this monitoring to try to identify early diagnostic markers.
[quote=&#8221;center&#8221;]Remote monitoring using digital sensors offers a solution to identify individuals around the world with early signs of ALS who could then be referred for evaluation by an ALS specialist. This work will have a very real impact and accelerate the research being conducted by our team at MGH and others.[/quote] 
The open innovation concept aims to spur progress among researchers, artificial intelligence engineers, and neurologists to find early digital diagnostic markers to promote early therapeutic intervention as well as family planning.
&#8220;A key barrier in early diagnosis for ALS is that at-risk individuals may be located far from specialized academic neurology centers and traveling for regular in-person examinations may be burdensome,&#8221; said Mark Garret, MD, director of DIALS and PREVENT ALS at MGH, two programs studying people with ALS-associated mutations.
&#8220;Remote monitoring using digital sensors offers a solution to identify individuals around the world with early signs of ALS who could then be referred for evaluation by an ALS specialist. This work will have a very real impact and accelerate the research being conducted by our team at MGH and others,&#8221; Garret added.
Scientists interested in participating in the initiative, or who seek more information, may send an email to neurolens@everythingals.org.
EverythingALS is a citizen-led nonprofit research organization that seeks to transform ALS through artificial intelligence and machine learning. Founded in 2014 by philanthropist Leandro P. Rizzuto, ALS Finding a Cure supports scientific efforts to end ALS.

Tag: grant

Coave wins grant to advance gene therapy CTx-TFEB for ALS

$400K ALS Association grant will advance CSF-1R inhibitor program

Dewpoint wins grant to develop its condensate-modifying therapies

ALS Association helping to move ORY-4001 into animal studies

New $400K grant aims to help ID digital diagnostic markers in ALS