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.

MIT researchers (from left to right) Hyungeun Song, Guillermo Herrera-Arcos, and Hugh Herr have developed the first “living” implant that uses rewired sensory nerves to revive paralyzed organs.  This is a part of The Yang Tan Collective developed at the K. Lisa Yang Center for Bionics at MIT Read more>> While it's not HSP-specific research and is still in early stages, the bladder application is explicitly on the researchers' radar. It is designed to help a paralyzed bladder not spastic/overactive bladder. Published in MIT News March 2026.

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 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.

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.

He 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.  Hopefully they can set up a California clinic.  This site has a ton of great links. 

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.