Ann Blackford

By

College: Medicine

HIV/AIDS Drugs Could Be Repurposed to Treat Age-Related Macular Degeneration; Study Published Today in Science

Published: Nov 20, 2014

LEXINGTON, Ky. (Nov. 20, 2014) – A landmark study published today in the journal Science by an international group of scientists, led by the laboratory of Dr. Jayakrishna Ambati, professor and vice chair of the Department of Ophthalmology & Visual Sciences at the University of Kentucky, reports that HIV/AIDS drugs that have been used for the last 30 years could be repurposed to treat age-related macular degeneration (AMD), as well as other inflammatory disorders, because of a previously undiscovered intrinsic and inflammatory activity those drugs possess.

 

AMD is a progressive condition that is untreatable in up to 90 percent of patients and is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have invaded the retina. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are no approved treatments for dry AMD thus far.

 

Nucleoside reverse transcriptase inhibitors (NRTIs) are the most widely used class of anti-HIV drugs. NRTIs are thought to be therapeutic in HIV/AIDS patients because they target the enzyme reverse transcriptase, which is critical for replication of HIV. Previous work from the Ambati lab found that a type of toxic molecule called Alu RNA accumulate in the retina to cause dry AMD; interestingly, Alu RNA and HIV are similar in that they both require reverse transcriptase to fulfill their life cycle. 

 

In their Science publication, Fowler et al. report that multiple FDA-approved NRTIs prevented retinal degeneration in a mouse model of dry AMD. Surprisingly, this effect of NRTIs in the eye was not due to the well-known function of these drugs to inhibit reverse transcriptase. Instead, NRTIs blocked an innate immune pathway called the “inflammasome”, even in experimental systems in which the NRTIs were not capable of blocking reverse transcriptase. 

 

In their report, they also showed that NRTIs were effective in other disease models that share common signaling pathways with the dry AMD model, including the “wet” form of AMD - a disease that when treated still does not lead to substantial vision improvement in two-thirds of patients - and graft-versus-host disease which is the major obstacle preventing successful allogeneic hematopoietic stem cell transplantation. 

 

"Repurposing of NRTIs could be advantageous, for one, because they are very inexpensive. Moreover, through decades of clinical experience, we know that some of the drugs we tested are incredibly safe. Since these NRTIs are already FDA-approved, they could be rapidly and inexpensively translated into therapies for a variety of untreatable or poorly treatable conditions," said Benjamin Fowler, the lead author and a postdoctoral fellow in the Ambati lab. Ambati added, “We are excited at the prospect of testing whether NRTIs could be effective in halting the progression of AMD in patients.”

 

NRTIs were originally designed to treat cancer in the 1960s. They re-emerged in the late 1980s and became the first drugs FDA-approved to treat HIV/AIDS.

 

This study was funded by the National Institutes of Health.

 

 

 

MEDIA CONTACT: Ann Blackford at 859-323-6442 or ann.blackford@uky.edu, or Kristi Lopez at 859-806-0445. 

 

fowler_1.jpgfowler_2.jpgfowler_3.jpgfowler_4.jpg
August
 
1
UK Writing Center Open for Summer Session 2 (June 9-August 4)
Mon
2
UK Writing Center Open for Summer Session 2 (June 9-August 4)
Tue
3
UK Writing Center Open for Summer Session 2 (June 9-August 4)
Wed
4
UK Writing Center Open for Summer Session 2 (June 9-August 4)
End of the Summer II 2016 Eight-Week Session
Thu
5
 
Fri
6
 
Sat
7
 
Sun
8
 
Mon
9
 
Tue
10
 
Wed
11
 
Thu
12
 
Fri
13
Parent and Families Open House
Sat
14
 
Sun
15
 
Mon
16
UK Women's Forum Board Meeting
Tue
17
 
Wed
18
 
Thu
19
K Week Kick-off
Off-campus Freshmen Check-in
Parent and Families Reception
Fri
20
New Student Induction Ceremony
Big Blue U
Getting Around Campus and Beyond
Campus Ruckus
Sat
21
UK Lex-Mart
K Team Lunch
Late-night Target Run
Sun
22
TEAL Classrooms Open House
TEAL Classrooms Open House
TEAL Classrooms Open House
TEAL Classrooms Open House
Dinner with your K Team
Mon
23
We Are UK
TEAL Classrooms Open House
TEAL Classrooms Open House
TEAL Classrooms Open House
TEAL Classrooms Open House
Campus Tours for K Teams
Tue
24
First Day of School Photos
First day of classes of Fall 2016
Wed
25
Pedalpalooza
First Day of School Photos
Thu
26
OCSS Wildcat Block Watch
Fri
27
Louis Zoellar Bickett: Saving Myself
Red River Gorge Adventure Trip for Out-of-State Students
Music Workshop for Teachers and Students: Michael Chandler
Flight 5191 Tenth Anniversary Memorial Service
Sat
28
Louis Zoellar Bickett: Saving Myself
Sun
29
Louis Zoellar Bickett: Saving Myself
Mon
30
Louis Zoellar Bickett: Saving Myself
Last Day to Add a Class for Fall 2016
Last Day to Withdraw to Receive 80% Refund
Tue
31
Louis Zoellar Bickett: Saving Myself
Wed
 
 
 
Aug 24
First Day of School Photos 08/24/2016

Thu, 08/25/2016

Fri, 08/26/2016

Sat, 08/27/2016 - Sun, 11/27/2016

Reset Page