Assistant Professor Steven Lenhert, Department of Biological Science, Florida State University
Photo Credit: Florida State University
Cancer treatments are costly and often difficult to prescribe. Steven Lenhert, a Florida State University assistant professor of biological science, believes the solution to rising costs and impersonal care lies in small plate the size of a computer chip — and he has the research to back it up.
Florida State University April/May 2012, (TALLAHASSEE) — New technology being developed at Florida State University could significantly decrease the cost of drug discovery, potentially leading to increased access to high-quality health care and cancer patients receiving personalized chemotherapy treatments.
The details, which are spelled out in a recent publication of the journal Biomaterials, outline the work of Steven Lenhert, a Florida State biology assistant professor and principal investigator on the research effort.
“Right now, cancer patients receive chemotherapy treatments that are based on the accumulated knowledge of what has worked best for people with similar cancers,” Lenhert said. “This is the case because hospitals don’t have the technology to test thousands of different chemotherapy mixtures on the tumor cells of an individual patient. This technology could give them access to that capability, making the treatments truly personalized and much more effective.”
Cancer treatments are costly and often difficult to prescribe. Steven Lenhert, a Florida State University Assistant Professor of Biological Science, believes the solution to rising costs and impersonal care lies in small plate the size of a computer chip-and he’s got the research to back it up.
The key to Lenhert’s invention is miniaturizing the first phase of a process used by pharmaceutical companies to discover new drugs. Right now, these companies use large, specialized laboratories to test hundreds of thousands of compounds on different cell cultures in a process known as high throughput screening. The equipment and manpower cost is substantial, even though only a tiny fraction of the compounds will ever make it to the next phase of testing.
Lenhert’s technology miniaturizes that process by printing all of the compounds on a single glass surface and testing them on cells using an innovative technique involving liposome microarrays, which are basically collections of drug-containing oil drops on a surface. If fully employed in the pharmaceutical industry, this technology would make the cost of this expensive process a thousand times cheaper, creating the potential for personalized cancer treatments, lower-cost medicine and more affordable, higher-quality health care options.
“In looking at the first phase of the drug-discovery process, it struck me how, in this age of extreme miniaturization, we are still using rooms full of robots and equipment to test drug compounds,” Lenhert said. “It reminded me of the early days of computers where you needed huge, room-spanning pieces of hardware to do the most mundane tasks. I said, ‘There has to be a better way.'”
Lenhert’s nanotechnology has been demonstrated as a proof of concept on a small scale with cells commonly grown in university laboratories. His research group is now working on scaling their technology up to the high levels needed to achieve medically relevant benefits. For personalized medicine applications, the “lab on a chip” technology could then be applied to cells obtained from patients through biopsies so doctors can determine which drugs will work on a particular patient. Depending on funding, Lenhert expects that the technology could be made commercially available after two years of development.
“We have taken an important first step in making liposome microarray technology viable for the pharmaceutical and medical industries,” said Aubrey Kusi-Appiah, a graduate student in Lenhert’s research group and first author on the published work. “We have established that it can be done.”
Drug effectiveness on common diseases Not all drugs are equally effective in all patients. Some types of drugs, such as analgesics, are effective on almost all patients, whereas other types, such as anticancer agents, are effective only on 25% of patients. In working towards the realization of personalized medicine, it is important to develop ways of using genetic information to prescribe to patients the most suitable drugs in light of their genetic risk to side effects. (Credit: Copyright : RIKEN)
ScienceDaily.com, April/May 2012 — The RIKEN Center for Genomic Medicine is examining how drugs can be matched to a patient’s genetic information through the study of single nucleotide polymorphisms. Taisei Mushiroda from the Laboratory for Pharmacogenetics explains…
Drugs are not equally effective on all patients. A treatment that is dramatically effective on some patients can be ineffective on others. Drugs can also have serious side effects; in the worst case, a drug used to treat a disease can produce a fatal outcome. By examining genetic differences among individuals and administering drugs on the basis of such findings, the impact of side effects can be reduced. Taisei Mushiroda, the Laboratory Head of the Research Group for Pharmacogenomics at the RIKEN Center for Genomic Medicine, is making advances in personalized medicine with research into how drugs can be tailored to a patient’s genetic information through the analysis of single nucleotide polymorphisms (SNPs).
Identifying the single nucleotide polymorphism (SNP) that plays a key role in drug rash
Japan’s Ministry of Health, Labor and Welfare announced that the gout treatment allopurinol, the antiepileptic drug carbamazepine and the analgesic, anti-inflammatory, antipyretic drug loxoprofen hold the highest incidence of serious drug rash.
“The data we collected showed that the great majority of drug rash cases were caused by carbamazepine. We therefore proceeded to clarify the relationship between carbamazepine and drug rash, using Genome- Wide Association Study (GWAS). We divided our study population into two groups: those who experienced side effects and those who did not. We performed a comprehensive analysis of single nucleotide polymorphisms (SNPs) on the genome to statistically extract SNPs that are significantly associated with drug rash. The gene involved in drug rash was then identified from among those positioned near the SNPs”
Strands of DNA carry genetic information in the sequenced arrangement of the four bases A (adenine), T (thymine), G (guanine) and C (cytosine). Consisting of some three billion base pairs, the human genome carries the complete genetic information of a human being. Although there is more than 99% base sequence homology in all people, the remaining 1% of base sequences differ individually. “These differences are SNPs. It is estimated that more than 10 million SNPs are present in the human genome. They are associated with the appearance and constitution of the individual, and even with how drugs work and what side effects develop.”
Relationship between drug rash caused by the antiepileptic drug carbamazepine and the HLA-A*3101 gene
Mushiroda and his colleagues conducted a study on Japanese epileptic patients undergoing treatment with carbamazepine. Of the sixty-one patients who experienced drug rash, 37 (about 61%) were found to have the HLA- A*3101 gene. In contrast, of the 376 patients who did not experience drug rash, 329 (about 88%) were found to lack HLA-A*3101.
“Reportedly, about 3% of Japanese patients experience drug rash when taking carbamazepine. About 60% of those have HLA-A*3101. It is therefore recommended that 60% of 3% (about 2%) of Japanese epileptic patients take antiepileptic drugs other than carbamazepine. In this way, the incidence of drug rash can be reduced by 2%,” says Mushiroda. However, as this association was only discovered in 2010, further evidence must be presented before it can be useful in a clinical setting.
Personalized medicine expected to find clinical applications in 1 or 2 years
The next step after identifying the associated SNP is to determine its applicability in the clinical setting. It is also necessary to verify that SNP diagnosis is effective in both therapeutic and cost-benefit aspects. In ongoing prospective clinical research of nevirapine, it has been estimated that SNP diagnosis would cut annual medical expenditures by about US$60,000 (about ¥5 million) per hospital. This next phase will be necessary for successful application of the new system to the antiepileptic drug carbamazepine.
Before SNP genotyping can be firmly established in medical practice, however, a quick and accurate method to examine SNPs at the lowest cost is needed. In collaboration with Toppan Printing Co. Ltd. and RIKEN Genesis Co. Ltd., Mushiroda’s team have developed the TPSA-003 genotype analysis system which can help to deliver more economical SNP genotyping (Fig. 3). The system provides results automatically in just one hour, simply by placing a single drop of untreated blood in the dedicated container and inserting the sample in the machine. “This is a groundbreaking machine. The conventional method involves the complex process of separating leukocytes from the blood sample, extracting the DNA from the leukocytes and applying the DNA to the machine to analyze SNPs. Conventionally, DNA extraction alone requires at least half a day even when undertaken by a highly skilled person. With the new system, the same task, including SNP genotyping, is completed in 60 minutes. This means that an accurate diagnosis can be obtained while the patient stays in the waiting room. Quick diagnosis is a big advantage for the patient as well.”