Home » Rare diseases » The gene therapy journey for rare diseases

Dr. Anis H. Khimani

Senior Strategy and Portfolio Leader, Life Sciences, PerkinElmer, Inc.

Glen Molotnikov

Strategy Leader, Biotherapeutics Discovery, Life Sciences, PerkinElmer, Inc.

Rare diseases (RD) impact an estimated 300 million people worldwide with 30 million of those in Europe.1New advances in gene therapy offer us a chance to treat rare diseases in a different way.

There are approximately 7,000 different rare diseases of which 4,100 are monogenic diseases.2 Monogenic diseases arise from a single gene mutation. Historically, treatment of these diseases has focused on treating the symptoms of the disease. However, with the recent advances in the field of gene therapy, opportunity now exists to correct the mutation causing the disease. Correcting the gene offers a potential therapeutic path to a little over half the known rare diseases.

Rare disease identification

The journey begins with elucidation of the genetic markers of the disease, which is accomplished via a concerted effort at an individual’s whole genome at single or multiple variant level. This is achieved through next generation sequencing (NGS) techniques which employs gene panels to detect changes at the genetic level.

Alternately, genotyping array technology is utilised to identify a select set of variants termed single nucleotide polymorphisms (SNPs) that are single or point mutations at genomic DNA level. They can potentially lead to a rare disease manifestation. A tremendous volume of genetic sequence data is analysed, annotated, and managed via an infrastructure of bioinformatics that eventually enables gene family clustering (e.g., hierarchical analysis), as well as patient stratification at population level.

More recently, artificial intelligence (AI), with its deep-learning capabilities has been applied to diagnosis, research, and drug discovery and development to treat RD. AI offers the potential to integrate data from patient demographics, diagnostics, and other critical information to drive therapeutic development.3

Disease biology and therapeutic strategies

Understanding the genetic basis of the disease can be more effectively driven via partnerships between academia, clinical researchers and industry. During the early discovery phase the primary goal for the researcher is to understand the biology of the specific disease and validate the molecular target(s).

One of the trending therapeutic approaches, gene therapy, involves the delivery of the corrected gene into the patient. There are primarily four different methods of gene delivery: naked DNA or RNA that is injected directly; physical delivery done through pressure, injection or a process called electroporation by which the DNA or RNA enters the cells through electrical stimulation; chemical vehicles such as lipids or polymers that form a sphere which deliver the genes into a cell; and the most common and well-studied are some viral vectors. Other factors that need evaluation are stability of the inserted or edited gene, as well as the immune response to the vectors.

Multiple applications of gene therapy

The principle behind gene therapy involves: understand the gene you are targeting, synthesise a DNA or RNA to correct the mutation and create a vehicle that will deliver the transgene to the faulty cells or tissue. Once this is accomplished for one type of disease the gene can be replaced with a different gene to target a similar condition.

With increased awareness of the genetics surrounding rare diseases, innovative technologies for precise identification and diagnostics, as well as gene therapy approaches to cure the disease, have fostered attention and a roadmap to address challenges.

International multi-stakeholder collaboration

Global as well as country level initiatives such as EURORDIS have led to programmes with significant funding, resulting in the establishment of centres of excellence and programmes needed to study the genetic and epidemiological basis of RD.

In addition, an increasing number of patient enrolment for clinical trials from gene and cell-based therapies will drive a concerted effort between clinical researchers, medical care providers and recipients.

Greater collaborative efforts between academia, technology innovators, therapeutic companies, regulatory agencies and non-profit organisations will lead to a unified front for RD. It will leverage opportunities and address challenges to unfold the next era of molecular medicine.

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PerkinElmer creates the instruments, tests and software used by scientists, researchers and clinicians to address the most critical challenges across science and healthcare. Through its comprehensive portfolio, the Company serves four market segments to help customers: Diagnostics, Life Sciences, Food, and Applied Markets. 

1 https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases
| 2 Ehrhart, Friederike, et al. “History of Rare Diseases and Their Genetic Causes – a Data Driven Approach.” BioRxiv, Jan. 2019, www.biorxiv.org/content/10.1101/595819v1.
| 3 Brasil, Sandra et al. “Artificial Intelligence (AI) in Rare Diseases: Is the Future Brighter?.” Genes vol. 10,12 978. 27 Nov. 2019, doi:10.3390/genes10120978.

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