Dr. Ari Zimran - A lifetime dedicated to a single-molecule disease

There are two types of treatment for this condition [2]:

1) Enzyme Replacement Therapy (ERT), with administration of recombinant glucocerebrosidase (such as Cerezyme®, Vpriv® and Elelyso®, all of which Dr. Zimran helped test in clinical trials), which allows for the breakdown of glucocerebroside.

2) Substrate Reduction Therapy (SRT), that aims to reduce the amount of glucocerebroside in the cells through the administration of substances which inhibit enzymes necessary to the production of glucocerebroside (such as Zavesca® and Cerdelga®, also tested by Dr. Zimran).

More recently, Professor Zimran has been investigating the connection between GBA1 mutations and Parkinson’s disease: patients with Gaucher’s disease, as well as carriers of GBA1 mutations, have been found to be predisposed to developing Parkinson’s disease.

The loss of function of the enzyme glucocerebrosidase compromises lysosomal degradation of α-synuclein, a protein which regulates synaptic vesicle trafficking and, therefore, involved in the control of neurotransmitter release. The accumulation of aberrant, soluble forms of this protein creates a neurotoxic environment [3]; this is aggravated by Gaucher’s disease, since glucocerebroside possesses the ability to stabilize these soluble oligomers, further potentiating the formation of amyloids and Lewy bodies and so, the progression of Parkinson’s disease. Moreover, these α-synuclein oligomers have the power to inhibit glucocerebrosidase, therefore creating a vicious cycle of progression of both Gaucher’s disease and Parkinson’s disease. [2]

Professor Zimran is also investigating the use of ambroxol (a drug which was initially used as a mucolytic) in patients with Gaucher’s disease. It is thought that it can be a pharmacological chaperone for this ailment (chaperone therapy consists of the administration of small molecule compounds which can specifically bind to misfolded glucocerebrosidase and help it fold correctly, allowing it to function normally) [4]. In a paper from May 2021, Professor Zimran and the other authors present some rather promising results, with clinical improvement observed in 25 patients.[5]

Other of Dr. Zimran’s areas of interest are the development of oral enzyme replacement therapy and gene therapy for Gaucher’s Disease.

Professor Zimran has a truly outstanding career, filled with accomplishments, and therefore it will undoubtedly be a privilege to attend his lecture and be able to experience his knowledge first-hand.