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Alzheimer's & Brain Awareness Month Spotlight: How Amphista Therapeutics is Tackling Neurological Disorders
<!doctype html><html lang="en"><head> <meta charset="utf-8"> <title>Alzheimer's & Brain Awareness Month Spotlight: How Amphista Therapeutics is Tackling Neurological Disorders</title> <link rel="shortcut icon" href="https://oxfordglobal.com/hubfs/OXFORD_GLOBAL-LOGO_SYMBOL.jpg"> <meta name="description" content="To honour Alzheimer's & brain awareness month, this article will acknowledge Amphista Therapeutics' use of targeted protein degradation (TPD) to treat symptoms of neurological disorders."> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta property="og:description" content="To honour Alzheimer's & brain awareness month, this article will acknowledge Amphista Therapeutics' use of targeted protein degradation (TPD) to treat symptoms of neurological disorders."> <meta property="og:title" content="Alzheimer's & Brain Awareness Month Spotlight: How Amphista Therapeutics is Tackling Neurological Disorders"> <meta name="twitter:description" content="To honour Alzheimer's & brain awareness month, this article will acknowledge Amphista Therapeutics' use of targeted protein degradation (TPD) to treat symptoms of neurological disorders."> <meta name="twitter:title" content="Alzheimer's & Brain Awareness Month Spotlight: How Amphista Therapeutics is Tackling Neurological Disorders"> <style> a.cta_button{-moz-box-sizing:content-box !important;-webkit-box-sizing:content-box !important;box-sizing:content-box !important;vertical-align:middle}.hs-breadcrumb-menu{list-style-type:none;margin:0px 0px 0px 0px;padding:0px 0px 0px 0px}.hs-breadcrumb-menu-item{float:left;padding:10px 0px 10px 10px}.hs-breadcrumb-menu-divider:before{content:'›';padding-left:10px}.hs-featured-image-link{border:0}.hs-featured-image{float:right;margin:0 0 20px 20px;max-width:50%}@media (max-width: 568px){.hs-featured-image{float:none;margin:0;width:100%;max-width:100%}}.hs-screen-reader-text{clip:rect(1px, 1px, 1px, 1px);height:1px;overflow:hidden;position:absolute !important;width:1px} </style> <link rel="stylesheet" href="https://oxfordglobal.com/hs-fs/hub/8696823/hub_generated/template_assets/135726131582/1732113079147/git/og-stage/css/main.min.css"> <link rel="stylesheet" href="https://cdn.oxfordglobal.com/fontawesome/6.5.1/css/fontawesome.min.css"> <link rel="stylesheet" href="https://cdn.oxfordglobal.com/fontawesome/6.5.1/css/brands.min.css"> <link rel="stylesheet" href="https://cdn.oxfordglobal.com/fontawesome/6.5.1/css/solid.min.css"> <!-- Editor Styles --> <style id="hs_editor_style" type="text/css"> #hs_cos_wrapper_module_17019620504109 { display: block !important; margin-bottom: 0px !important } </style> <!-- Added by GoogleAnalytics4 integration --> <script> var _hsp = window._hsp = window._hsp || []; window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} var useGoogleConsentModeV2 = true; var waitForUpdateMillis = 1000; if (!window._hsGoogleConsentRunOnce) { window._hsGoogleConsentRunOnce = true; gtag('consent', 'default', { 'ad_storage': 'denied', 'analytics_storage': 'denied', 'ad_user_data': 'denied', 'ad_personalization': 'denied', 'wait_for_update': waitForUpdateMillis }); if (useGoogleConsentModeV2) { _hsp.push(['useGoogleConsentModeV2']) } else { _hsp.push(['addPrivacyConsentListener', function(consent){ var hasAnalyticsConsent = consent && (consent.allowed || (consent.categories && consent.categories.analytics)); var hasAdsConsent = consent && (consent.allowed || (consent.categories && consent.categories.advertisement)); gtag('consent', 'update', { 'ad_storage': hasAdsConsent ? 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Dementia is the name for a group of symptoms associated with an ongoing decline of brain functioning. This neurodegenerative disease impacts memory, thinking skills, and other cognitive abilities. <a href="https://www.nhs.uk/conditions/alzheimers-disease/" rel="noopener" target="_blank"><span style="color: #4a6ee0;">Alzheimer's affects every 1 in 14 people over the age of 65</span></a>. There is currently no cure, which is fuelling the growing demand for effective therapies.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"><strong>Treating Neurodegenerative Diseases using PROTACs</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Tau protein plays a key role in neuronal cells to maintain their cell shape and provide routes for the transport of cargo proteins. In Alzheimer's disease, <a href="https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease#:~:text=In%20Alzheimer's%20disease%2C%20however%2C%20abnormal,the%20synaptic%20communication%20between%20neurons" rel="noopener" target="_blank"><span style="color: #4a6ee0;">abnormal chemical changes cause tau to detach from microtubules and bind to other tau molecules, forming tangles inside neurons</span></a>. This accumulation of tau protein blocks the neuron's transport system, which hinders synaptic communication between neurons.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Targeted protein degraders trigger a cell's natural disposal system to remove disease-causing proteins and provide hope of treating diseases previously thought to be undruggable. Degrading rather than inhibiting a target protein offers several advantages such as <a href="https://www.dundee.ac.uk/cetpd/about#:~:text=Targeted%20protein%20degradation%20co%2Dopts,immunology%2C%20neuroscience%20and%20respiratory%20diseases" rel="noopener" target="_blank"><span style="color: #4a6ee0;">a more efficacious drug response at lower doses and a more precise intervention with less risk of side effects and disease resistance</span></a>.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"><strong>Case Study</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Amphista Therapeutics is a biotechnology company focused on developing a pipeline of central nervous system <span>(</span>CNS<span>)</span> drugs. The company recently announced new data demonstrating in vivo efficacy of its mechanistically differentiated targeted protein degraders.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Cereblon and von Hippel-Lindau (VHL) proteins are two most common E3 ligases recruited by PROTACs to induce TPD. However, Amphista's degraders use a different protein degrading mechanism to degrade BRD9 proteins, which play a role in chromatin remodelling and regulation of transcription. Amphista Therapeutics' <a href="https://amphista.com/amphista-therapeutics-unveils-new-differentiated-mechanism-of-action-for-brd9-degradation-at-2024-protein-degradation-in-focus-symposium/" rel="noopener" target="_blank"><span style="color: #4a6ee0;">degrader selectively induces BRD9 to DCAF16 proximity and acts as molecular glue</span></a>, leading to the rapid degradation of BRD9.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"><strong>Related: </strong></p> <ul> <li><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/university-of-pennsylvania-and-fast-to-develop-aav-gene-therapy-for-angelman-syndrome" rel="noopener" target="_blank"><span style="color: #4a6ee0;">University of Pennsylvania and FAST to Develop AAV Gene Therapy for Angelman Syndrome</span></a></span></li> <li><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/small-molecule-targets-toxic-rna-linked-to-als-and-dementia" rel="noopener" target="_blank"><span style="color: #4a6ee0;">Small Molecule Targets Toxic RNA Linked to ALS and Dementia</span></a></span></li> <li><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/new-class-of-molecular-glues-could-reshape-cancer-drug-discovery" rel="noopener" target="_blank"><span style="color: #4a6ee0;">New Class of Molecular Glues Could Reshape Cancer Drug Discovery</span></a></span></li> </ul> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Data from proteomic and genetic validation studies demonstrate that Amphista's bifunctional degraders facilitate the degradation of BRD9 by target-assisted E3 ligase recruitment. This unique mechanism selectively induces the proximity of BRD9 to DCAF16, serving as a molecular glue.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Amphista's <a href="https://www.fiercebiotech.com/research/amphista-claims-its-targeted-protein-degraders-have-rapid-efficacy-against-tumor-and-cns" rel="noopener" target="_blank"><span style="color: #4a6ee0;">degraders have demonstrated sustained degradation of target-protein and anti-tumour efficacy</span></a>. They demonstrated a statistically significant decline in tumour burden and survival advantages in several in vivo disease models.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Further data showed that Amphista's degraders demonstrated <a href="https://amphista.com/amphista-therapeutics-announces-new-data-demonstrating-in-vivo-efficacy-and-cns-activity-of-its-mechanistically-differentiated-targeted-protein-degraders/" rel="noopener" target="_blank"><span style="color: #4a6ee0;">statistically significant protein degradation when compared with over 8000 other proteins including closely related homologs when dosed at 100 times half-maximal degradation concentration (DC50</span></a><span><span style="color: #4a6ee0;">)</span></span>. Amphista also claims that its therapies carry a lower risk of tumour resistance.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">Beverly Carr, Interim CEO of Amphista Therapeutics added: "The last six months have been transformative for Amphista and these new compelling <em>in vivo</em> data strengthen our belief that our technology has the potential to deliver differentiated protein degrader molecules with class-leading physicochemical properties, enabling us to target a wider tissue and indication scope than traditional protein degrader approaches."</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"><strong>Conclusion</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; padding-left: 0cm;">This case study shows Amphista's commitment to brain health. Although the FDA has not yet approved Amphista's targeted protein degraders, early results are promising. Amphista anticipates that its therapies will be able to penetrate to CNS across multiple targets. 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