Proteomic analysis reveals early pathological defects in corticospinal motor neurons of a spastin model of hereditary spastic paraplegia, which are improved by NU-9 treatment.  By Dr. Gautam, ... Silverman, Baas, Ozdinler. 

Article search: Neurobiology of Disease 227 (2026) 107494

Modeling Spastic Paraplegia 4 with Corticospinal Motor Neuron-enriched Cortical Organoids Reveals Genotype-phenotype and HDAC6-targetable Pathway - published in Cell Reports March 2026.  

Unveiling HDAC6: A Promising Therapeutic Target for SPG4 - Insights for Human and Animal Models.  Too much of the protein called HDAC6 damages the microtubules and contributes to nerve fiber degeneration.  Mutant M1-spastin-induced HDAC6 hyperactivation is the key pathogenic culprit. Blocking HDAC6 with the drug Tubastatin restored microtubles, prevented nerve fiber damage, and improved movement problems in mice with SPG4.  HDAC6 inhibition restored microtubule acetylation (resilience) and rescued axonal degeneration in Motor Cortical Organoids.  HDAC6 inhibition improves Corticospinal Tract integrity and gait deficiency in SPG4 mice.

Intracerebroventricular (injecting drugs into the brain's cerebral ventricles) SPAST-AAV9 Gene Therapy Prevents Manifestation of Symptoms in a Mouse Model of SPG4 Hereditary Spastic Paraplegia - published in ResearchGate Nov. 2025. 

They used micro RNA to stop the expression from the SPAST gene and cDNA to express healthy human M1 and M87 in mouse pups.  Treatment replaced endogenous spastin with healthy spastin preventing the onset and progression of corticospinal degeneration and gait defects.

Their findings show that CRL-4 contributes to spastin stability regulation and that it is possible to induce spastin recovery and rescue of SPG4-HSP defects by blocking CRL-4-mediated spastin degradation.  The druggable pathway regulates spastin stability in preclinical models that inhibit the pathway which prevents spastin degradation, leading to higher spastin levels and reduced phenotypic defects. Sardina, Carsetti, Giorgini, etc. (2024) Article: PMID: 38551087

He is furthering research with Dr. Ozdinler on AKV-9 (formally called NU-9). The FDA cleared AKV-9 for clinical trials. Dr. Silverman created AKAVA Therapeutics, a drug company, for AKV-9 to be produced.  AKV-9 has proven successful for distributing NU-9 to treat ALS and Alzheimers Disease.  But that's not all...

AKV9 works by targeting the accumulation of misfolded proteins, a core issue in neurodegenerative diseases like ALS and Alzheimer's, helping cells clear these toxic protein clumps, improving neuron health, and restoring cellular machinery like the ER and mitochondria, though the exact binding site is still being explored. It helps the cell's recycling system (lysosomes) break down harmful protein aggregates, rather than just preventing folding, by facilitating their removal and improving cellular structure.  It may also work for other diseases, so our fingers are crossed.

Look here for HSP/PLS studies underway or upcoming.

This Australian charity is organized by volunteers to find treatments for HSP that are highly effective, widely available, and readily affordable.   They were established in 2005.

They have lots of resources in the Tecnology section.

The National Library of Medicine and the National Center for Biotechnology Information compose research studies here.  Look up studies here, or look for a trial you may want to take part in.

Dr. Fakhari leads the Spastic Paraplegia - Centers for Excellence Research Network  (SP-CERN).  They have eleven locations across America to research and assist those living with spastic paraplegia.  SP-CERN received $8.4 million for 5 years of research so we can expect great things to be coming.  They are researching people with HSP to create clinical ready groups for trials.   

Watch Dr. Feng Zhang, a Biochemist Professor at MIT, explain how he developed TIGR-Tas which goes beyond CRISPER Cas9.  Dr. Zhang explains how TIGR-Tas can repair or replace defective RNA sequences by hijacking the spliceosome machinery — correcting at the mRNA level without permanently altering genomic DNA.  He is very engaging and a delight to listen to.  

This American site is partenred with the Carter Foundation for Neurologic Research on the east coast of America for childhood SPG3A 

This foundation was created by parents whose SPG4 children are de novo.  They have leading research, resources, and welcome donations.

This Canadian website was developed by an Ontario family to fund research with gene therapy for childhood SPG4 and other diseases.

They are devoted to increasing awareness and funding research for childhood SPG4.

Dr. Darius Ebrahimi-Fakhari (head of SP CERN) is listed as one of their research doctors.  The site is devoted to limiting/ending SPG4 with the NULISA biomarker study (2026) and a HSP cattle study (2025).

They organized International HSP Day in the Netherlands in 2026!  Use the link to view their 4 hours of interviews with researchers, patients, therapists ect. The first 2 hours are in Dutch (with English subtitles) and the next 2 hours are in English (with Dutch subtitles) here:  https://schoon-producties.webinargeek.com/watch_ondemand/k47ph4Ul2TKPpPsWlT9uqiRu8ZOKD-0A5KorwN9I03M/.   They have some research directed at SPG11 & SPG15. 

They are devoted to research for KIF1A associated neurological disorders. SPG30 is caused by variants in the KIF1A gene.  KIF1A is listed by Global Genes as an advocacy group for SPG30.

This Boston based organization funds research for SPG47, SPG50, SPG51, and SPG52.

This Canadian group is devoted to finding a cure via gene therapy, protein replacement therapy, and/or drug repurposing for SPG50.

Researchers from the US, Canada, and Brazil work together to make progressions for people with HSP SPG76.