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<a href="https://acurastem.com/">AcuraStem</a> has secured nearly $7 million in grant funding from the National Institutes of Health (NIH) and the Department of Defense (DOD) to accelerate the development of therapies for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) and related diseases.
Coming on the heels of a <a href="https://alsnewstoday.com/news/takeda-acquires-license-als-therapy-aimed-toxic-tdp-43/">$580 million deal with Takeda</a>, which obtained an exclusive, worldwide license to AcuraStem&#8217;s investigational therapies that target the PIKfyve enzyme, the new funding, awarded via a peer-review process, will help the company advance several other programs toward clinical trials.
&#8220;We are thrilled to receive continued support from NIH and the DOD,&#8221; Sam Alworth, MS, AcuraStem&#8217;s co-founder and CEO, said in a <a href="https://www.prnewswire.com/news-releases/acurastem-secures-7-million-in-funding-support-from-nih-and-dod-to-accelerate-therapies-for-als-and-ftd-302048227.html">company press release</a>. &#8220;Leaders from the scientific community selected AcuraStem for these awards through a rigorous peer-review process, which demonstrates the excellence of our research.&#8221;
Nearly all ALS patients, including those with <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic</a> or <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial ALS</a>, accumulate a misfolded version of the TDP-43 protein in nerve cells. Normally found inside the nucleus, abnormal TDP-43 forms clumps outside it, which disrupts the function of motor neurons, the nerve cells that control voluntary movement.
The Takeda deal covers therapies, including AS-202, which is designed to target and block PIKfyve. Blocking this enzyme activates <a href="https://acurastem.com/therapeutics">multivesicular body (MVB) exocytosis</a>, a process that removes waste and unwanted proteins from cells.
By activating this process, AS-202 should promote the clearance of abnormal TDP-43 and prevent the neurodegeneration that marks ALS and frontotemporal dementia (FTD), a related condition also caused by TDP-43 clumping.
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<h3 class="p1"> Funding covers other therapeutic programs</h3>
The NIH and DOD funding will also advance the development of therapies that target UNC13A and SYF2, programs not covered by the Takeda licensing agreement.
Inside the nucleus, TDP-43 normally acts as an RNA-binding protein involved in processing messenger RNA (mRNA), an intermediary molecule produced as part of protein production.
When abnormal TDP-43 moves outside the nucleus, it disrupts the processing of UNC13A mRNA, leading to a loss of the UNC13A protein. This loss, which is worsened by mutations in the UNC13A gene, is associated with reduced survival in ALS and FTD patients.
The company&#8217;s iNeuroRx platform, which couples patient-derived disease models with human genetic data, was able to replicate UNC13A-related disease in patient neurons, according to AcuraStem.
Building on these findings, the company has developed antisense oligonucleotides (ASOs), a class of DNA/RNA-binding small molecules that prevent the disruption of UNC13A mRNA processing by TDP-43, thereby restoring UNC13A function.
These advances offer &#8220;a promising therapeutic approach for TDP-43 proteinopathies [protein-clumping diseases] and a deeper understanding of UNC13A&#8217;s role in disease progression,&#8221; AcuraStem wrote in its release.
The company says it&#8217;s also discovered that SYF2, another protein in the nucleus that&#8217;s involved in mRNA processing, is a potential ALS target. SYF2 regulates mRNA processing, which is affected by the movement of TDP-43 out of the nucleus. Modulating SYF2 may address both the toxic buildup of TDP-43 and counter the widespread dysregulation of genes, including UNC13A.
&#8220;Targeting SYF2 could offer a more direct and potentially effective therapeutic strategy compared to addressing each dysregulated gene individually,&#8221; AcuraStem noted.

Tag: ALS therapy

AcuraStem awarded NIH, DOD grants to boost ALS therapies