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Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.” 
Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.”
Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.”