Genetics, Gene Therapy & Genetic Disease

In round spermatids, SPINK2 is necessary to inactivate the acrosin during its transit through the endoplasmic reticulum and the Golgi apparatus.

In the absence of SPINK2, acrosin can auto‐activate, disorganize the Golgi apparatus, prevent the production of the acrosome and induce a block at the round spermatid stage.

A reduced amount of SPINK2 in heterozygotes is also deleterious, inducing a milder phenotype of oligozoospermia and/or teratozoospermia without a systematic infertility.

By methodological advances chain length distribution (CLD) and phosphorylation of glycogen were determined in brain tissue confirming that overexpressed wild‐type laforin corrects the molecular phenotype in an LD mouse model.

Phosphatase‐inactive laforin does not correct glycogen hyperphosphorylation in malin‐ and laforin‐deficient mice and prevents abnormal CLD and accumulation of glycogen as well as LB formation.

Prevention of abnormal chain length distribution and accumulation of brain glycogen as well as LB formation by phosphatase‐inactive laforin is malin‐dependent as no rescue occurs in malin‐deficient mice.

General impairment of autophagy is not necessary in LD as markers of autophagic flux are not changed in any of our LD mouse models.

Laforin controls glycogen chain length distribution in a malin‐dependent fashion, and lack of this control leads to abnormal glycogen structure, glycogen accumulation, LB formation, hence to LD.

DOK7 gene therapy suppresses motor nerve terminal degeneration at the neuromuscular junction (NMJ) and muscle atrophy in ALS model mice.

DOK7 gene therapy prolongs lifespan and enhances motor activity in ALS model mice.

DOK7 gene therapy, or any equivalent method that stably and safely enlarges the NMJ, has potential for treating various motor neuron diseases that manifest NMJ defects.