Albert La Spada, MD, PhD, Receives 2025 Rare Disease Scholar Award

On Nov. 20, 2025, the Oxford-Harrington Rare Disease Centre (OHC) announced the recipients of the 2025 Rare Disease Scholar Award. Among the 10 recipients was Albert La Spada, MD, PhD, a Distinguished Professor of pathology and neurology in the UC Irvine School of Medicine. The award aims to help transform promising discoveries from academic labs into clinical practice, and OHC recognized La Spada for his work on a silencer RNA (siRNA) therapy for amyotrophic lateral sclerosis type 4 (ALS4).

“There are currently no treatments for ALS4, a rare, juvenile-onset familial genetic form of ALS,” says La Spada. “ALS4 patients suffer considerable disability due to limb weakness, severe muscle wasting and sensory dysfunction.”

ALS4 is caused by mutations in the senataxin (SETX) gene. Each ALS4 patient has two SETX genes, one of which is abnormal. “This project seeks to create an siRNA to prevent expression of the mutant SETX gene without affecting the normal, healthy gene,” says La Spada. “Because the vast majority of ALS4 patients all share the same disease mutation, it is possible to design a single siRNA that will recognize only the mutant, disease-causing SETX gene.”

The proposed allele-selective siRNA dosage reduction treatment represents a highly sophisticated therapy for the inherited neurological disorder. “We are proposing a disease-modifying therapy that should dramatically slow the progression of this disabling motor neuron disease,” says La Spada, adding that patients might even have the potential to recover function.

La Spada is grateful to receive this award, which provides an advisory team offering advanced drug and business development support, $100,000 and the opportunity to compete for additional support and funding.

“Because ALS4 is quite rare, it is very difficult to obtain funding for this type of research,” says La Spada. “The Oxford-Harrington Rare Disease Scholar program is therefore critical for efforts to develop treatments for rare diseases such as ALS4.”

This award comes on the heels of La Spada receiving grant funding through the Robert Packard Center and ALS United on another project that could someday result in new therapeutic targets for ALS.

“The Packard Center – ALS United research project focuses on the role of altered TDP-43 function in ALS,” says La Spada, noting that virtually all forms of ALS, both sporadic (90% of cases) and familial (10% of cases, including ALS4), are characterized by dysfunction of TDP-43. “We will study how TDP-43 dysregulation causes improper processing of the end of an RNA transcript and how improper RNA processing can alter RNA function, resulting in the demise and death of motor neurons in ALS.”

Both the award and grant support continued research in treating this debilitating disease. “Patient management consists of purely supportive care,” says La Spada. “We’re working to translate RNA-based research into improved patient outcomes.”