TAU researchers develop new treatment for rare genetic disorder

Written on |

Adolescents and young adults with familial adenomatous polyposis bear a high risk of developing cancer

Researchers from Tel Aviv University and Tel Aviv Sourasky Medical Center (Ichilov Hospital) have developed an innovative drug treatment for familial adenomatous polyposis (FAP), a rare, inherited condition that affects adolescents and young adults and often leads to colorectal cancer. The novel drug, based on antibiotics, inhibits the development of intestinal polyps that, left untreated, become cancerous. In a preliminary clinical trial, the condition of seven out of eight patients who completed the full treatment improved dramatically. The research was jointly led by Prof. Rina Rosin-Arbesfeld of the Department of Microbiology and Clinical Immunology at TAU’s Sackler School of Medicine and Prof. Revital Kariv of the Sackler School and the Department of Gastroenterology at Tel Aviv Sourasky Medical Center. FAP, which is characterized by multiple polyps along the gastrointestinal tract, especially in the large bowel, is caused by a mutation in the adenomatous polyposis coli (APC) gene. These mutations are also crucial for colorectal cancer development.

Why does FAP lead to colon cancer?

“To prevent the development of colorectal cancer, FAP patients are closely monitored via frequent colonoscopies to locate and remove their polyps,” Prof. Rosin-Arbesfeld says. “However, some patients must have their colons removed at a very young age, which dramatically affects their quality of life.” In its normal state, APC promotes the production of a protein that inhibits cancer development. But mutations to the APC gene produce an inactive protein that is unable to prevent the development of the polyps. In some FAP patients, the mutations in the APC gene are what are called “nonsense mutations.” “Each sequence of three nucleotides in the DNA is a code that tells the cell to produce a certain amino acid, which are the building blocks of the proteins produced in the body’s cells,” Prof. Rosin-Arbesfeld explains. “At the end of the protein coding sequence, there is usually a ‘stop codon’ to stop the protein production. But in FAP patients with a nonsense mutation, the APC’s stop codon appears prematurely, so the protein production stops prematurely, creating an inactive protein.”

Preventing surgical intervention

Previous experiments on cell cultures and mouse models in Prof. Rosin-Arbesfeld’s laboratory revealed that certain types of antibiotics caused cells to “ignore” the mutation stop codon and a normal protein resulted. These trials yielded promising results that led to the clinical trial at Tel Aviv Sourasky Medical Center. “Since the relevant antibiotics were already approved for human use, we decided to move directly from the laboratory to the clinic and to examine the treatment of FAP patients,” says Prof. Rosin-Arbesfeld. In the clinical study carried out by Prof. Kariv and Dr. Shlomi Cohen, director of the Pediatric Gastroenterology Unit at Dana-Dwek Children’s Hospital, 10 FAP patients received the novel antibiotic therapy. Eight of them completed the treatment, which lasted four months. Colonoscopies performed during and after the treatment showed that in seven patients the polyps significantly decreased in number. Moreover, the positive effects of the treatment were evident a year after it began. “Our goal as therapists, in addition to preventing cancer, is to improve the quality of life of our patients and their families and to enable them to live as full and normal lives as possible,” Prof. Kariv concludes. “The new therapeutic approach we are developing may allow patients to delay surgical intervention or even prevent it entirely.” The researchers recently won Tel Aviv University’s SPARK grant, which supports the development of applied research.

Related posts

Tiny Robot Navigates in Physiological Environment and Captures Targeted Damaged Cells

28 March 2023

Hyperbaric Treatment More Effective than Medicines for Fibromyalgia Caused by Head Injury

24 March 2023

Promoting Women in Medicine

9 March 2023

#TAU_WOMEN_POWER

7 March 2023

Researchers Discover Mechanism that Facilitates Formation of Brain Metastases

27 February 2023

Light Pollution is Killing Desert Rodents

10 February 2023

Three Tel Aviv University Researchers Awarded the ERC Proof of Concept (PoC) grants

9 February 2023

Researchers Identify A New Genetic Risk Factor for Age-related Eye Disease

8 February 2023

People With Autism Experience Pain at a Higher Intensity

31 January 2023

Researchers Uncover New Factors Linked to Williams Syndrome

24 January 2023

Lessons in Tolerance and DNA Extraction in Tel Aviv University’s Medical Labs

18 January 2023

Medical Clowns – No Laughing Matter

18 January 2023

Tel Aviv University’s First MedTech Hackathon Sets a High Bar

15 January 2023

Researchers use Smartwatches to Measure Safety of COVID Vaccine

28 December 2022

Tel Aviv University Establishes Multidisciplinary Center for Research of Autoimmune Diseases

18 December 2022

Breakthrough in the Field of Controlled Drug Delivery

16 December 2022

Victoria

Tok Corporate Centre, Level 1,
459 Toorak Road, Toorak VIC 3142
Phone: +61 3 9296 2065
Email: office@aftau.asn.au

New South Wales

Level 22, Westfield Tower 2, 101 Grafton Street, Bondi Junction NSW 2022
Phone: +61 418 465 556
Email: davidsolomon@aftau.org.au

Western Australia

P O Box 36, Claremont,
WA  6010
Phone: :+61 411 223 550
Email: clivedonner@thelinqgroup.com